Table 1.
Targets for Hp infection treatment.
| Target | Pathway | Reference |
|---|---|---|
| Metabolism | ||
| Type II 3-dehydroquinase dehydratase (DHQ2) | Shikimate pathway | [30,31,32,33] |
| Shikimate 5-dehydrogenase (SDHase) | Shikimate pathway | [30,33] |
| Shikimate kinase (SK) | Shikimate pathway | [30,33,34] |
| Chorismate synthase | Shikimate pathway | [30,33] |
| Phosphopantetheine adenylyltransferase (PPAT) | Coenzyme A biosynthesis | [35,36] |
| Carbon starvation protein A | Starvation response, utilization of peptides, and host–pathogen interactions | [37] |
| Methylthiotransferase (MiaB) | Protein synthesis | [37] |
| Ribosomal RNA small subunit methyltransferase E | Protein synthesis | [37] |
| Ribosomal protein L11 methyltransferase | Protein synthesis | [37] |
| Tetrapyrrole (Corrin-Porphyrin) methylase family protein | Protein synthesis | [37] |
| Peptide chain release factor 1 | Protein synthesis | [37] |
| Fumarate reductase (FrdA, FrdB, and FrdC) | Krebs cycle and anaerobic respiration | [33,38] |
| Glu-tRNAGln amidotransferase, subunits A (GatA), B (GatB), and C (GatC) | Protein synthesis | [26,33] |
| Helicase-nuclease DNA Repair Enzymes (AddAB) | DNA damage reparation | [39,40] |
| Cytochrome C-type biogenesis protein CcdA | Cytochrome C synthesis | [37] |
| Cytochrome C oxidase, subunits CcoN, CcoO, CcoP and CcoQ | ATP synthesis | [37] |
| Flavodoxin (Fld) | Oxidative decarboxylation of pyruvate | [28,41,42,43] |
| Pyruvate:ferredoxin oxidoreductase (POR), subunit α (porA), β (porB), ϒ (porC or porG) and δ (porD) | Oxidative decarboxylation of pyruvate | [26,33,44,45,46] |
| Flavodoxin:quinone reductase (FqrB) | Oxidative decarboxylation of pyruvate | [33,42,46] |
| 2-oxoglutarate:acceptor oxidoreductase, subunits A (OorA), B (OorB), C (OorC) and D (OorD) | Succinyl-CoA production | [26,33,45] |
| Cell Wall Structure | ||
| N-succinyl-L,L-diaminopimelic acid desuccinylase, SDAP-deacylase (DapE) | Succinylase pathway (lysine biosynthesis) | [17,47,48] |
| Glutamate racemase MurI | Peptidoglycan biosynthesis | [49,50] |
| Multi-drug resistance protein MsbA | Lipopolysaccharide biosynthesis | [51] |
| UDP-galactose 4-epimerase (GalE) | Lipopolysaccharide biosynthesis | [52] |
| pH Homeostasis | ||
| Urease, subunits α (UreA), and β (UreB) | Acclimation to low pH | [33,53,54,55,56,57,58] |
| Nickel-responsive regulator (NikR) | Urease expression and nickel uptake regulator | [53,54] |
| Nickel–cobalt transporter (NixA) | Nickel/cobalt transport | [54,59,60] |
| Urease accessory protein UreE | Urease maturation | [33,54,59,61,62,63] |
| Urease accessory protein UreF | Urease maturation | [54,61,62] |
| Urease accessory protein UreG | Urease maturation | [33,54,62,63] |
| Urease accessory protein UreH | Urease maturation | [54,61] |
| Hydrogenase/urease maturation factor (HypA) | Urease maturation | [61,63] |
| Hydrogenase/urease maturation factor (HypB) | Urease maturation | [61,63] |
| Heat Shock Protein A (HspA) | Nickel homeostasis | [59,64,65] |
| Hpn | Nickel homeostasis and storage | [59,61,64] |
| Acid-activated urea channel (UreI) | Urea permeability | [33,66] |
| α-carbonic anhydrase | Acclimation to low pH | [33,67,68,69,70,71] |
| β-carbonic anhydrase | Acclimation to low pH | [33,67,68,69,71,72] |
| Virulence (Adherence, Motility and Pathogenicity) | ||
| Spore coat polysaccharide biosynthesis protein C (PseC) | Pseudaminic acid biosynthesis pathway (Pse): flagellin glycosylation | [33,73,74] |
| Heat-inducible transcription repressor (HrcA) | Flagella biosynthesis | [37] |
| Transcriptional repressor of DnaK operon (HspR) | Flagella biosynthesis | [37] |
| Major flagellin FlaA | Flagellar filament composition | [33,53,75,76,77] |
| Minor flagellin FlaB | Flagellar filament composition | [53,75,76,77] |
| Flagellar hook-associated protein 2 (FliD) | Flagellum assembly (filament capping) | [33,76,77] |
| Flagellar hook-associated protein 1 (FlgK) | Flagellum assembly (hook-filament junction formation) | [33,76,77,78] |
| ATP-binding protein (YlxH) | Flagella biosynthesis | [33,79] |
| Flagellar basal body L-ring protein (FlgH) | Flagellum assembly (L-ring composition) | [33,77] |
| Flagellar basal body P-ring protein (FlgI) | Flagellum assembly (P-ring composition) | [33,77] |
| Flagellar basal body M-ring protein (FliF) | Flagellum assembly (MS ring composition) | [33,77] |
| Flagellar biosynthetic protein (FliP) | Flagellum assembly (Flagellar export component) | [33,60,77] |
| Flagellar biosynthetic protein (FliQ) | Flagellum assembly (Flagellar export component) | [33,77] |
| Flagellar motor switch protein (FliY) | Flagellum assembly (C-ring composition; Flagellar export component) | [33,77] |
| Flagellum-specific ATP synthase (FliI) | Flagellum assembly (Flagellar export component) | [33,77] |
| Flagella-specific σ factor (FliA) | Flagellum assembly (regulatory protein) | [53,77] |
| FlgM (putative antagonist of FliA) | Flagellum assembly (regulatory protein) | [53,77] |
| Cytotoxin-associated gene A (CagA) | cag pathogenicity island (host cell metabolism modulation, inflammation, metaplasia and precancerous transformations) | [80,81,82,83] |
| cag-Type IV secretion system (T4SS) | cag pathogenicity island (translocation of bacterial factors (e.g., Cag A and peptidoglycan) into host cells) | [80,83] |
| HopQ adhesin (outer membrane protein) | Adhesion to host cells and translocation of CagA into host cells | [84] |
| Vacuolating cytotoxin (VacA) | Cellular vacuolation, apoptosis and inhibition of cell cycle progression and host immune response | [81,82,85,86] |
| Blood group antigen binding adhesin (BabA) | Adhesion to host cells | [80,81,82] |
| High temperature requirement A (HtrA) | Chaperone and proteolytic activities (intercellular adhesion cleavage) | [37,85,87] |
| Sialic acid-binding adhesin (SabA) (outer membrane protein) | Bacterial migration to epithelium surface | [76,88] |
| HopZ adhesin (outer membrane protein) | Adhesion to host cells | [76,80,85] |
| OipA adhesin (outer membrane protein) | Adhesion to host cells | [76,80,85] |
| AlpA/B adhesin (outer membrane protein) | Adhesion to host cells | [76,80,85] |
| Active Efflux of Metal Ions | ||
| Cation efflux system protein CusA | Efflux of cobalt/zinc/cadmium | [37] |
| Cobalt/Zinc/Cadmium efflux system membrane fusion protein | Efflux of cobalt/zinc/cadmium | [37] |
| Cobalt/Zinc/Cadmium resistance protein (CzcA, CzcB and CzcC) | Efflux of cobalt/zinc/cadmium | [37,89] |
| CznABC metal efflux pump | Efflux of cadmium/zinc/nickel | [89] |
| Ferrix siderophore transport system TonB periplasmic binding protein | Iron transport | [37] |
| Ferric siderophore transport system ExbB biopolymer transport protein | Iron transport | [37,60] |
| Haemin uptake system ATP binding protein | Iron transport | [37] |
| Protection Against Stress | ||
| Glutathionyl spermidine synthetase | Intracellular thiol redox balance regulation | [37] |
| Iron-binding ferritin-like antioxidant protein | Prevention of toxic reactive species formation | [37] |
| DNA-binding protein Dps | DNA breaking protection | [37] |
| Superoxide dismutase | Superoxide dismutation | [37] |
| Thioredoxin reductase | Prevention of toxic reactive species formation | [37] |
| RNA polymerase σ54 factor | Survival under stress conditions | [33,90] |
| Multi-drug resistance protein MsbA | Efflux of hydrophobic drugs | [33,51] |
| Exodeoxyribonuclease (LexA) | SOS response activation | [33,91] |
| Homeostatic stress regulator (HsrA) | Regulation of gene expression | [92,93,94,95] |